Neonatal Hyperoxia Contributes Additively to Cigarette Smoke–Induced Chronic Obstructive Pulmonary Disease Changes in Adult Mice

McGrath‐Morrow, Sharon A.; Lauer, Thomas; Collaco, Joseph M.; Yee, Min; O’Reilly, Michael A.; Mitzner, Wayne; Neptune, Enid; Wise, Robert A.; Biswal, Shyam

doi:10.1165/rcmb.2010-0259oc

Cited by 24 publications

(23 citation statements)

References 33 publications

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“…This is in contrast to what we recently found in adult mice previously exposed to neonatal hyperoxia. In that study, we found that neonatal hyperoxia exposure contributed additively to CS-induced COPD-lung changes in the adult mouse [38]. Several reasons may explain the differences.…”

Section: Discussionmentioning

confidence: 99%

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

McGrath‐Morrow¹,

Malhotra

Lauer³

et al. 2011

Experimental Lung Research

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The impact of early childhood cigarette smoke (CS) exposure on CS-induced chronic obstructive pulmonary disease (COPD) is unknown. This study was performed to evaluate the individual and combined effects of neonatal and adult CS exposure on lung structure, function, and gene expression in adult mice. To model a childhood CS exposure, neonatal C57/B6 mice were exposed to 14 days of CS (Neo CS). At 10 weeks of age, Neo CS and control mice were exposed to 4 months of CS. Pulmonary function tests, bronchoalveolar lavage, and lung morphometry were measured and gene expression profiling was performed on lung tissue. Mean chord lengths and lung volumes were increased in neonatal and/or adult CS-exposed mice. Differences in immune, cornified envelope protein, muscle, and erythrocyte genes were found in CS-exposed lung. Neonatal CS exposure caused durable structural and functional changes in the adult lung but did not potentiate CS-induced COPD changes. Cornified envelope protein gene expression was decreased in all CS-exposed mice, whereas myosin and erythrocyte gene expression was increased in mice exposed to both neonatal and adult CS, suggesting an adaptive response. Additional studies may be warranted to determine the utility of these genes as biomarkers of respiratory outcomes.

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Section: Discussionmentioning

confidence: 99%

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

McGrath‐Morrow¹,

Malhotra

Lauer³

et al. 2011

Experimental Lung Research

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“…Ten randomly chosen areas from each lung section were photographed with the 10x objective of a Nikon Eclipse 80i microscope (Nikon Instruments Inc., Melville, NY) as previously described. 3 Mean airspace chord length (MCL) was measured from each image using NIS-Elements AR (Nikon Instruments Inc., Melville, NY). The software allowed for manual identification and exclusion of large airways and vessels prior to MCL calculations.…”

Section: Methodsmentioning

confidence: 99%

“…However, exposure to hyperoxia can impair alveolar growth during a critical period of postnatal lung development and lead to structural and functional changes in the mature lung. 1,2,3 Exposure to hyperoxia has also been shown to be major risk factor for the development of chronic lung disease of prematurity also known as bronchopulmonary dysplasia (BPD). 4 …”

Section: Introductionmentioning

confidence: 99%

“…7 Hyperoxic-exposure in the neonatal mouse can cause inhibition of alveolar growth similar to that found with BPD, through induction of p21 and p53 cell cycle regulatory genes. 23,89–11 We previously have shown that neonatal mice with Nrf2 null mutations have increased lung inflammation and decreased survival when exposed to hyperoxia. 12 Since alveolar growth inhibition and airway inflammation are characteristic features of BPD, we were also interested in understanding the temporal impact of Nrf2 activation on cell cycle regulatory gene expression.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status

McGrath‐Morrow¹,

Lauer²,

Collaco³

et al. 2014

Cytokine

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Hyperoxia exposure can inhibit alveolar growth in the neonatal lung through induction of p21/ p53 pathways and is a risk factor for the development of bronchopulmonary dysplasia (BPD) in preterm infants. We previously found that activation of nuclear factor erythroid 2 p45-related factor (Nrf2) improved survival in neonatal mice exposed to hyperoxia likely due to increased expression of anti-oxidant response genes. It is not known however, whether hyperoxic induced Nrf2 activation attenuates the growth impairment caused by hyperoxia in neonatal lung. To determine if Nrf2 activation modulates cell cycle regulatory pathway genes associated with growth arrest we examined the gene expression in the lungs of Nrf2−/− and Nrf2+/+ neonatal mice at one and three days of hyperoxia exposure. Methods Microarray analysis was performed in neonatal Nrf2+/+ and Nrf2−/− lungs exposed to one and three days of hyperoxia. Sulforaphane, an inducer of Nrf2 was given to timed pregnant mice to determine if in utero exposure attenuated p21 and IL-6 gene expression in wildtype neonatal mice exposed to hyperoxia. Results Cell cycle regulatory genes were induced in Nrf2−/− lung at one day of hyperoxia. At 3 days of hyperoxia, induction of cell cycle regulatory genes was similar in Nrf2+/+ and Nrf2−/− lungs, despite higher inflammatory gene expression in Nrf2−/− lung. Conclusion p21/ p53 pathways gene expression was not attenuated by Nrf2 activation in neonatal lung. In utero SUL did not attenuate p21 expression in wildtype neonatal lung exposed to hyperoxia. These findings suggest that although Nrf2 activation induces expression of antioxidant genes, it does not attenuate alveolar growth arrest caused by exposure to hyperoxia.

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“…QRT-PCR was performed using the Applied Biosystems (Foster City, CA) TaqMan assay system, as previously described [13]. Probes and primers were designed and synthesized by Applied Biosystems.…”

Section: Methodsmentioning

confidence: 99%

The innate immune response to lower respiratory tract E. Coli infection and the role of the CCL2-CCR2 axis in neonatal mice

et al. 2017

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Neonates have greater morbidity/mortality from lower respiratory tract infections (LRTI) compared to older children. Lack of conditioning of the pulmonary immune system due to limited environmental exposures and/or infectious challenges likely contributes to the increase susceptibility in the neonate. In this study, we sought to gain insights into the nature and dynamics of the neonatal pulmonary immune response to LRTI using a murine model. Methods Wildtype (WT) and Ccr2−/− C57BL/6 neonatal and juvenile mice received E. coli or PBS by direct pharyngeal aspiration. Flow cytometry was used to measure immune cell dynamics and identify cytokine-producing cells. Real-time PCR and ELISA were used to measure cytokine/chemokine expression. Results Innate immune cell recruitment in response to E. coli-induced LRTI was delayed in the neonatal lung compared to juvenile lung. Lung clearance of bacteria was also significantly delayed in the neonate. Ccr2−/− neonates, which lack an intact CCL2-CCR2 axis, had higher mortality after E. coli challenged than Ccr2+/+ neonates. A greater percentage of CD8+ T cells and monocytes from WT neonates challenged with E. coli produced TNF compared to controls. Conclusion The pulmonary immune response to E. coli-induced LRTI differed significantly between neonatal and juvenile mice. Neonates were more susceptible to increasing doses of E. coli and exhibited greater mortality than juveniles. In the absence of an intact CCL2-CCR2 axis, susceptibility to LRTI-induced mortality was further increased in neonatal mice. Taken together these findings underscore the importance of age-related differences in the innate immune response to LRTI during early stages of postnatal life.

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Neonatal Hyperoxia Contributes Additively to Cigarette Smoke–Induced Chronic Obstructive Pulmonary Disease Changes in Adult Mice

Cited by 24 publications

References 33 publications

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status

The innate immune response to lower respiratory tract E. Coli infection and the role of the CCL2-CCR2 axis in neonatal mice

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